Accelerating Global Deletion of the Abnormal Toxicity Test (ATT) and of the Target Animal Batch Safety Test (TABST) - AFSA

The ATT and the TABST are old safety test used respectively in human and veterinary vaccine production, the roots of which can be traced back to the beginning of the XX century to testing for phenol preservatives. The test has no analytical component: it is a pass/fail quality procedure in which mice or guinea pigs are injected many times the human dose of vaccine, and then followed to see whether abnormal reactions are observed. In the absence of alternative strategies to ensure safety, ATT and TABST have become in the course of an entire century de facto standards, required for decades by every pharmacopoeia in the world, a role they have maintained even in light of ever mounting evidence of their poor scientific foundation, and later confirmation of their demonstrated irrelevance. The WHO’s Expert Committee on Biological Standardization itself weighted in the matter, issuing in 2018 its recommendation that ATT be ignored whenever mentioned in WHO documents (Lei D, et al., Removal of the innocuity test from The International Pharmacopoeia and WHO recommendations for vaccines and biological products. Biologicals. 2020 Jul; doi: 10.1016/j.biologicals.2020.05.003.).

A number of pharmacopoeias have finally proceeded to ATT deletion (e.g. Europe, USA, Canada, Japan, Brazil, Argentina, and partially India – see the full list in the table below), and almost every country in the world have either deleted or waived TABST, with some important exceptions. A number of countries are considering granting waivers to their use, and/or deletion, supported by manufacturers, for which ATT and TABST represent extra costs, extra risks (due to their inherent variability which can make safe batches fail the test), and are not applicable to newer vaccines designed from the start for different, non-animal based safety testing strategies.

For the many countries where ATT and TABTS are still considered irreplaceable tests and ultimate guarantors of vaccines safety, their elimination requires appropriate engagement of local authorities, with exchange of information on the successful deletions already achieved in other countries/regions, and trust building. The discussion needs to be prompted and fostered, consider barriers and difficulties still hindering the elimination of the tests, enriched by the participation of key international stakeholders and experts which can contribute experiences and expertise, and help resolve doubts and assuage fears, to help regulators embrace change and produce actionable items to bring forward the elimination of the tests.